The present application relates generally to sterilization of medical apparatus using both hydrogen peroxide vapor as sterilant and a glow discharge. The glow discharge (plasma) when activated within the sterilization chamber contributes to the sterilization and decomposes the sterilant at the end of a sterilization program. The glow discharge however the must be properly controlled otherwise undesired surface etching may occur on the sensitive medical apparatus. This application describes a novel plasma control method and apparatus which minimize the harmful side effects plasma on the medical apparatus during a sterilization program.
Note that the points discussed below may reflect the hindsight gained from the disclosed inventions, and are not necessarily admitted to be prior art.
Some background information can be found in the following documents, all of which are hereby incorporated by reference: Beatriz Unger-Bimczok, Volker Kottke, Christian Hertel, Johannes Rauschnabel, “The Influence of Humidity, Hydrogen Peroxide Concentration, and Condensation on the Inactivation of Geobacillus stearothermophilus Spores with Hydrogen Peroxide Vapor”, Journal of Pharmaceutical Innovation, Vol. 3, No. 2 (28 Jun. 2008), pp. 123-133; James R. Rickloff “Factors Influencing Hydrogen Peroxide Gas Sterilant Efficacy”, Advanced Barrier Inc. Nov. 12, 2008; U.S. Pat. Nos. 4,169,123, 4,169,124, 4,643,876, 4,756,882, 4,956,145, 4,642,165, and 4,744,951; PCT application WO 2005/067984; the Sterrad NX Sterilizer user and service manuals (from Advance Sterilization Products); and the Sterrad 100S Sterilizer user manual and service manuals.
Medical instruments were traditionally sterilized either with heat, such as is provided by steam, or a chemical, such as formaldehyde or ethylene oxide in the gas or vapor state. Each of these methods has drawbacks. Many medical devices, such as fiberoptic devices, endoscopes, power tools, etc. are sensitive to heat, moisture, or both. Formaldehyde and ethylene oxide are both toxic gases that pose a potential hazard to healthcare workers. Problems with ethylene oxide are particularly severe, because its use requires long aeration times to remove the gas from articles that have been sterilized. This makes the sterilization cycle time undesirably long.
Sterilization using liquid hydrogen peroxide solution has been found to require high concentration of sterilant, extended exposure time and/or elevated temperatures. However, sterilization using hydrogen peroxide vapor has been shown to have some advantages over other chemical sterilization processes (see, e.g., the '123 and '124 documents cited above).
The combination of hydrogen peroxide with a plasma provides certain additional advantages, as disclosed in the '876 document cited above. The '882 document cited above discloses the use of hydrogen peroxide vapor, generated from an aqueous solution of hydrogen peroxide, as a precursor of the reactive species generated by a plasma generator. The combination of hydrogen peroxide vapor diffusing into close proximity with the article to be sterilized together with the reactive particles generated by plasma act together to sterilize the articles even more efficiently.
However, these methods of combining hydrogen peroxide vapor with a plasma, while useful in “open” systems, have been found to be inadequate to effect sterilization in articles having diffusion-restricted areas, since the methods are dependent upon diffusion of the sterilant vapor into close proximity with the article before sterilization can be achieved. Thus, in order to use these methods on articles with long, narrow lumens, it has been necessary to use high concentration of sterilant, extended exposure time, and/or elevated temperatures.
The sterilization of articles containing diffusion-restricted areas, such as long narrow lumens, presents a special challenge for hydrogen peroxide vapor that has been generated from an aqueous solution of hydrogen peroxide, because: (i) water (H2O) has a higher vapor pressure than hydrogen peroxide (H2O2), and will vaporize faster than hydrogen peroxide from an aqueous solution; (ii) water has a lower molecular weight than hydrogen peroxide and will diffuse faster than hydrogen peroxide in the vapor state.
Consequently, when an aqueous solution of hydrogen peroxide is vaporized, the innermost locations in a diffusion-restricted lumen will initially see an enhanced H2O:H2O2 ratio. This can lead to condensation of water vapor on the surface of the material to be sterilized before sufficient impingement of hydrogen peroxide has reached the innermost locations. The liquid-phase water then becomes a barrier to the penetration of hydrogen peroxide vapor into diffusion restricted areas, such as small crevices and long narrow lumens.
The '145 document cited above discusses the efficacy of highly concentrated hydrogen peroxide for the safe sterilization. The '067984 document discusses the problem of condensed water vapor blocking the diffusion of the sterilant to the bacteria lying on the surface of the material to be sterilized. The Unger document cited above explains the influence of humidity, hydrogen peroxide concentration, and the condensation of the water vapor in detail.
One cannot solve the problem by using more concentrated hydrogen peroxide, since concentrated solutions of hydrogen peroxide, i.e., greater than 60% by weight, can be hazardous, due to the oxidizing nature of the solution. Decomposition of liquid hydrogen peroxide is very exothermic, and releases large volumes of gas, so that stability is a serious concern. Highly concentrated liquid hydrogen peroxide is so energetic that it has been used as a monopropellant for rocket engines. Moreover, highly concentrated hydrogen peroxide can form unstable reaction products with minor contaminants (such as fingerprint grease), and those reaction products can be a further source of instability.
The above-cited documents '165 (Bier) and '951 (Cummings et al.) both attempt to address this problem. Bier attempts to solve the problem by metering small increments of a hydrogen peroxide solution onto a heated surface to ensure that each increment is vaporized before the next increment is added. This helps to eliminate the difference in the vapor pressure and volatility between hydrogen peroxide and water, but it does not address the fact that water diffuses faster than hydrogen peroxide in the vapor state.
Cummings describes a process for concentrating hydrogen peroxide from a relatively dilute solution of hydrogen peroxide and water and supplying the concentrated hydrogen peroxide in vapor form to a sterilization chamber. The process involves vaporizing a major portion of the water from the solution and removing the water vapor produced before injecting the concentrated hydrogen peroxide vapor into the sterilization chamber as shown in FIG. 1A.
FIG. 1A shows the apparatus proposed by Cummings, which includes a vaporizing chamber 7 having any well-known means 3 for injecting into chamber 7 a predetermined amount of a solution of hydrogen peroxide and water. Chamber 7 may be controllably heated by any well-known means. Chamber 7 has an outlet port 2 through which vapors may be exhausted from chamber 7 by means of a vacuum. Port 2 may be opened or closed by valve 1. Chamber 7 also has an outlet port 4 leading through passage 6 to a sterilization chamber 8. Passage 6 may be open or closed by valve 5.
The process is initiated by the injection into evacuated chamber 7 of predetermined amount of a liquid solution of hydrogen peroxide and water through injection means 3. When valve 5 is closed and valve 1 is open; vacuum is applied to chamber 7 to evacuate air. Chamber 7 is heated until the desired temperature within chamber 7 is reached; that temperature is such that, when taken with the pressure within chamber 7, a portion of water in the form of vapor will be forced to evaporate from a solution of liquid hydrogen peroxide solution present in chamber 7. Conditions are created within chamber 7 to cause the preferential vaporization of water from the solution and the vapor formed thereby is withdrawn from chamber 7 through port 2. At a point in time when a major portion of the water has been vaporized and withdrawn, but before a significant quantity of hydrogen peroxide has vaporized and been withdrawn, valve 1 is closed. What remains in chamber 7 is a hydrogen peroxide-water solution enriched in hydrogen peroxide, specifically greater than 40% hydrogen peroxide by weight, preferably 50 to 80% by weight. Vaporization of this enriched solution continues within chamber 7 and then valve 5 is opened to admit the vapors formed thereby to evacuated sterilization chamber 8. With a substantial amount of the water having been removed, the hydrogen peroxide vapor sterilant is able to disperse itself throughout the sterilizer and penetrate wraps and tubes without encountering a barrier effect that otherwise would have been present by reason of the effects of the present of water discussed above. Thus, the effective concentration of hydrogen peroxide vapor at the point of attack on the goods to be sterilized is markedly enhanced by the process.
Advance Sterilization Products, a division of Johnson and Johnson initially offered Sterrad 100S plasma sterilizer which use 59% wt hydrogen peroxide as sterilant.
Couple of years ago Advance Sterilization Products introduced the more advanced Sterrad 100NX Sterilizer which employs Cummings method of delivering hydrogen peroxide to sterilize devices within the sterilization chamber. In this apparatus a 59% wt aqueous solution of hydrogen peroxide is injected into the delivery system condenser where it is concentrated and then introduced into the chamber. This modified process concentrates the 59% hydrogen peroxide to above 80% nominal hydrogen peroxide (by selectively vaporizing and removing water) prior to being transferred into the sterilization chamber. Sterrad 100NX range have shorter sterilization cycles and higher lumen sterilization specifications.
Although Sterrad NX range provides sterilization efficacy recently some medical device manufacturers like Inutitive no longer recommends concentrated plasma sterilizers for their devices as they have reported that exposure to high concentration hydrogen peroxide vapor damages some of their endoscopes.
Further some sensitive endoscope manufacturers have required customized sterilization programs for their devices in order to minimize the sterilant vapor damage on their equipment.
The use of plasma to sterilize containers was suggested in U.S. Pat. No. 3,383,163. Plasma is an ionized body of gas which may be generated by the application of radio frequency power. The ionized gas will contact microorganisms on the surfaces of the items to be sterilized and effectively destroy the microorganisms. As mentioned above (006) the combination of hydrogen peroxide with a plasma provides certain additional advantages namely helping the sterilisation process by generating DNA destroying free radicals and UV light and at the end of the sterilization cycle by decomposing the harmful hydrogen peroxide sterilant.
Plasma generated at atmospheric pressure or at higher pressures are called “arcs” or high temperature plasma and may involve temperatures in excess of 1000.degree. C. Plasma generated at reduced pressures are called “glow discharge” or low temperature plasma and involve temperatures of a few tenths to a few hundred degrees centigrade (plasma glow because light is emitted as these excited neutral particles relax to a lower energy state). The low temperature plasma described in '876 is generated at pressures of less than 10 Torr and generally involves temperatures of less than 100 degree C.
The plasma power used in a sterilizer may be continuous or pulsed, that is, the power may be applied continuously to the plasma or the plasma may be pulsed by activating the power in a cyclic manner while maintaining the pressure of the plasma constant. The U.S. Pat. No. '876 describes a pulsed plasma to prevent the overheating of the gas within the chamber as well as preventing the overheating of objects that may be desired to be sterilized continuous plasma may be employed if there is little danger of overheating the item to be sterilized.
A plasma contains positive ions, electrons, neutral gas atoms or molecules, UV light and also excited gas atoms and molecules, which can carry a large amount of internal energy. All of these species can and do interact with any surface placed in contact with the plasma. By choosing the gas mixture, power, pressure etc. we can quite precisely tune, or specify, the effects of the plasma upon the surface. For this reason plasma is also widely used in the industry for etching purposes for silicon processing to PCB manufacturing (see http://en.wikipedia.org/wiki/Plasma_etching). For example the plasma etching method described U.S. Pat. No. 8,158,525 generally involves an etching step of placing, on a stage in a chamber, a substrate in which a prescribed mask pattern is formed by a protective film on a surface of a material to be etched, generating a plasma in the chamber while supplying processing gas to the chamber, and etching a portion of the material corresponding to an opening portion in the mask pattern. This etching occurs as a result of highly energised ions (usually heavy gas is preferred) bombarding a giving surface and damaging it. As stated above in the plasma process is employed in low temperature plasma sterilisers to sterilise sensitive medical apparatus by generating free-radicals and decomposing the harmful sterilant. However the resultant unavoidable etching as an unintended consequence needs to be minimized. Further many modern medical apparatus use materials based on polymers which under bombardment of energised ions could undergo physical changes and become more brittle etc losing its desirable properties for the task they were designed for.
The current invention disclose a novel method and an apparatus wherein: (i) the glow discharge plasma power is carefully profiled to execute the its task while minimize and etching damage. During the pre-conditioning plasma phase of a typical sterilisation cycle prior to exposing the medical apparatus to the sterilant the low pressure (54 FIG. 3) the vacuum within the sterilisation chamber contains pre-dominantly air molecules. During this phase plasma generates a controllable homogenous heat up to 55 degree C. and generates UV and free radicals which all contribute to the sterilisation. When the glow discharge is applied again at a later phase of the sterilisation program (64 in FIG. 3) the primary function of the plasma is to decompose the hydrogen peroxide and the secondary being to contribute to the sterilisation via the UV and free radicals generated. The current invention describes an methodology and an apparatus to maximise the above mentioned positive effects of the plasma during different phases of the sterilisation cycle while minimising its negative effect of causing a unintended etching on the medical apparatus to be sterilized. The said plasma power control is particularly challenging in the post sterilant diffusion phase as the RF generator output level applied must be sufficiently high to generate and sustain the plasma for generation of free radicals and more importantly the full decomposition of the sterilant hydrogen peroxide before opening of the door of the chamber but low enough to minimize and etching damage.
The U.S. Pat. No. '876 is silent on the etching however describes a method to control the power control output of the RF generator by turning the power of the generator in a pulsed sequence (the pulsing sequence is the ratio of power on to power off) which was varied over a range to prevent overheating any object. Said patent mentions a pulse sequence with a 1:2 pulsed plasma, power would be applied for 0.5 milliseconds and then turned off and applied again 1.0 milliseconds later.
The '876 patent however does not address the etching and polymer degeneration caused by the plasma in the sterilisation chamber. The pulsing in the method means turning the full power of the RF generator on and off. This continuous surge of power each time the plasma is retriggered would still generate bursts of high energy ions which continue stress the sensitive materials (polymers etc) used in medical apparatus and undesirable etching effect in all materials.
The current invention profiles the power of the RF generator in a manner to optimise its use in a low temperature sterilizer by
(i) employing a pulse width modulation to adjust the plasma power after the full power application to initiate an effective plasma state.
(ii) Monitoring the plasma within the chamber so that the glow discharge continuously present and re-initiate if it extinguished.
(iii) Applying different RF power characteristic when the gas content of the plasma is different phases of sterilisation process.